Islatravir

Islatravir (4′-ethynyl-2-fluoro-2′-deoxyadenosine, EFdA, or MK-8591) is an investigational drug for the treatment of HIV infection. It is classified as a nucleoside reverse transcriptase translocation inhibitor (NRTTI). Merck is developing a subdermal drug-eluting implant to administer islatravir.

In 2021, FDA placed a partial clinical hold for several studies under Islatravir. The reason was a decline in CD4 T cells under therapy. Merck announced to restart the study program in 2023 with a decreased dose, however studies of islatravir for pre-exposure prophylaxis (PrEP) will be discontinued.

In 2024, results from a phase II study combining islatravir with lenacapavir indicated that the regimen shows promise as a possible weekly oral regimen.

Biological activity
Islatravir has activity against HIV in animal models, and is being studied clinically for HIV treatment and prophylaxis. Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that unlike other such inhibitors, inhibits HIV through multiple mechanisms, providing rapid suppression of the virus, when tested in macaques and mice. Nevertheless, there are HIV strains resistant to islatravir and research is ongoing.